Inflammation Mediates Longitudinal Relations Between Common Psychiatric Disorder Severity and Future Executive Function Impairment

Abstract

Background: Scar models propose that elevated psychiatric disorder severity predisposes people to future decreased executive function (EF) through heightened inflammation. However, most prior research on this topic has been cross-sectional. We thus investigated if increased Time 1 (T1) common psychiatric disorder severity predicted Time 3 (T3) EF decrement via Time 2 (T2) inflammation in two unique samples. Methods: Community- dwelling adults participated in Study 1 (n = 614) and Study 2 (n = 945). Both studies measured T1 common psychiatric disorder severity (Composite International Diagnostic Interview–Short Form major depressive disorder, generalized anxiety disorder, and panic disorder severity scales), T2 inflammation (interleukin-6, C-reactive protein, and fibrinogen blood concentration), and T3 EF (Brief Test of Adult Cognition by Telephone). Structural equation modeling was conducted. Results: Greater T1 diagnostic severity predicted higher T2 inflammation (after 2 months in Study 1: Cohen’s d = 0.84; following 9 years in Study 2: d = 0.82). Moreover, higher T2 inflammation predicted lower T3 EF (after 18 months in Study 1: d = -1.30; following 9 years in Study 2: d = -1.18), with large effect sizes. Further, the mediation paths were significantly moderate-to-large in Study 1 (d = 0.76) and Study 2 (d = 0.69). Socio-demographic, lifestyle, medication use, and physical health variables did not moderate these mediation models. Conclusions: Inflammation may be a mechanism explaining the T1 common psychiatric disorder severity–T3 EF relation. Treatments that target inflammation and/or anxiety or depressive disorders may prevent some individuals from experiencing EF decline.